1. Field of the Invention
The present invention relates to a diagnostic method for stroke/asymptomatic cerebral infarction using polyamine or acrolein content, polyamine oxidase activity or protein content thereof as an indicator. Furthermore, the present invention relates to a screening method for patients with stroke/asymptomatic cerebral infarction using polyamine or acrolein content, polyamine oxidase activity or protein content thereof as an indicator.
2. Description of the Related Art
Cerebrovascular disease is the common cause of death next to malignant neoplasm and cardiac disease, and the annual loss of life number thereof is around 10 times of that of renal disease. Moreover, it causes such a tremendous trouble in daily life, for aftereffect of the disease accompanies paralysis and akinesia for example. Stroke constitutes a majority of the cerebrovascular diseases, and early detection and treatment of the disease are difficult. Furthermore, asymptomatic brain infarction that does not show any subjective symptoms is mostly detected accidentally by diagnostic imaging. So, in present circumstances, there have been no diagnostic markers available in blood or urine examination. Therefore, development of a simple and accurate diagnostic method, which does not require expensive medical equipments such as diagnostic imaging system, has been desired.
By the way, polyamine is biogenic amine that exists in the body universally, and spermine, spermidine or putrescine is the representatives. And these polyamines exist in high concentration in cells and act as cell growth factors by interacting with nucleic acids within the body. On the other hand, polyamine produces cytotoxic acrolein (CH2═CH—CHO) during its metabolic process. This acrolein is detoxified by aldehyde dehydrogenase in cells, but it shows intense toxicity when it leaks out of cells.
In addition, since polyamine accumulates in the plasma of patients with chronic renal failure, it is assumed that polyamine is one of the causative substances of uremia. Moreover, it is said that it is difficult to remove this polyamine by dialyses thoroughly. Thus, clarification the essence of polyamine-induced toxicity leads to the development of more effective therapeutic agents of uremia.
Based on this standpoint, the present inventors tried to inhibit polyamine oxidase, which acts in the pathway for the synthesis of acrolein from polyamine, by using amino guanidine. And as a result, it was confirmed that the polyamine lost its toxicity (Japanese Patent Publication No. 2002-281999). In diseases that involve tissue destruction, it is possible with high probability that polyamine liberated from cells receives oxidative deaminated by polyamine oxidase in plasma, then acrolein is formed in large quantities, so that the formed acrolein is associated with toxicity.